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4-Hydroxyisoleucine: A Potential New Treatment for Type 2 Diabetes Mellitus

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Abstract

4-Hydroxyisoleucine (4-HIL) is a compound found in Trigonella foenum-graecum (fenugreek) seeds, which have been used as part of traditional medicine to treat diabetes mellitus. The synthesis of 4-HIL on a large scale is possible using fermentation methods (artificial synthesis) involving the isolation of the l-isoleucine dioxygenase gene from Bacillus thuringiensis, which can yield a greater quantity of 4-HIL than that produced with conventional methods (82 % attained with fermentation methods vs. 0.6–39 % attained with conventional methods). In studies of rats and humans, T. foenum-graecum improved laboratory parameters associated with renal dysfunction and dyslipidemia, increased levels of antioxidants and hormones that are altered in patients with type 2 diabetes mellitus (T2DM), and decreased fasting blood glucose, 2-h postprandial plasma glucose, and glycated hemoglobin. Similarly, in in vitro and preclinical studies, 4-HIL decreased glucose levels, hepatic glucose production, glucose/insulin ratios, indicators of hepatic damage, triglycerides, and total cholesterol, and increased utilization of glucose and levels of high-density lipoprotein cholesterol. Studies in humans are needed to determine whether 4-HIL is safer and more effective than current medications for the treatment of T2DM.

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Author contributions

MIZ developed the concept for the review article and wrote the manuscript. FG provided guidance and performed the critical revision of the intellectual concept and content of the article. Both authors approved the final version of the article.

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Authors and Affiliations

  1. Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, People’s Republic of China

    Mohammad Ishraq Zafar & Feng Gao

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  1. Mohammad Ishraq Zafar
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  2. Feng Gao
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Correspondence to Feng Gao.

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MIZ and FG declare that they have no conflicts of interest.

Funding

This study was supported by Scientific Research Grants by Ministry of Education, P.R China. The funding organizations are public institutions and had no role in the concept and writing of the article and approval of the manuscript.

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Zafar, M.I., Gao, F. 4-Hydroxyisoleucine: A Potential New Treatment for Type 2 Diabetes Mellitus. BioDrugs 30, 255–262 (2016). https://doi.org/10.1007/s40259-016-0177-2

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